Abstract
The gut microbiota has been linked to various neurological disorders via the gut–brain axis. Diet influences the composition of the gut microbiota. The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet established for treatment of therapy-resistant epilepsy in children. Its efficacy in reducing seizures has been confirmed, but the mechanisms remain elusive. The diet has also shown positive effects in a wide range of other diseases, including Alzheimer’s, depression, autism, cancer, and type 2 diabetes. We collected fecal samples from 12 children with therapy-resistant epilepsy before starting KD and after 3 months on the diet. Parents did not start KD and served as diet controls. Applying shotgun metagenomic DNA sequencing, both taxonomic and functional profiles were established. Here we report that alpha diversity is not changed significantly during the diet, but differences in both taxonomic and functional composition are detected. Relative abundance of bifidobacteria as well as E. rectale and Dialister is significantly diminished during the intervention. An increase in relative abundance of E. coli is observed on KD. Functional analysis revealed changes in 29 SEED subsystems including the reduction of seven pathways involved in carbohydrate metabolism. Decomposition of these shifts indicates that bifidobacteria and Escherichia are important contributors to the observed functional shifts. As relative abundance of health-promoting, fiber-consuming bacteria becomes less abundant during KD, we raise concern about the effects of the diet on the gut microbiota and overall health. Further studies need to investigate whether these changes are necessary for the therapeutic effect of KD.
Highlights
The human gut microbiota has received increasing attention in recent years and numerous studies have demonstrated its role in health and disease
ketogenic diet (KD) is used in the treatment of therapy-resistant epilepsy and in neurometabolic disorders where glucose is not fully available as an energy substrate such as glucose transporter type 1 (GLUT1)
We examine how the fecal microbiome is affected by KD in children with epilepsy
Summary
The human gut microbiota has received increasing attention in recent years and numerous studies have demonstrated its role in health and disease. Diet influences the composition of the human gut microbiome.[6] Based on the anti-seizure effect of fasting, the ketogenic diet (KD), a high-fat, adequate-protein, very low-carbohydrate diet, was developed in the early 1920s7 to mirror the key metabolic effects of fasting. A diet very high in fat and low in carbohydrates induces multiple changes in the intermediary metabolism and results in the use of ketones as the main energy substrate. KD is used in the treatment of therapy-resistant epilepsy and in neurometabolic disorders where glucose is not fully available as an energy substrate such as glucose transporter type 1 (GLUT1). We have analyzed both taxonomic composition and functional profiles, i.e., gene content and pathway abundances in the gut microbiome during KD in children with therapy-resistant epilepsy using shotgun metagenomic sequencing
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